10:30 AM; no major effect that I notice throughout the day - it’s neither good nor bad. This smells like placebo (and part of my mind is going how unlikely is it to get placebo 3 times in a row!, which is just the Gambler’s fallacy talking inasmuch as this is sampling with replacement). I give it 60% placebo; I check the next day right before taking, and it is. Man!
The next morning, four giant pills’ worth of the popular piracetam-and-choline stack made me... a smidge more alert, maybe? (Or maybe that was just the fact that I had slept pretty well the night before. It was hard to tell.) Modafinil, which many militaries use as their “fatigue management” pill of choice, boasts glowing reviews from satisfied users. But in the United States, civilians need a prescription to get it; without one, they are stuck using adrafinil, a precursor substance that the body metabolizes into modafinil after ingestion. Taking adrafinil in lieu of coffee just made me keenly aware that I hadn’t had coffee.
When I spoke with Jesse Lawler, who hosts the podcast Smart Drugs Smarts, about breakthroughs in brain health and neuroscience, he was unsurprised to hear of my disappointing experience. Many nootropics are supposed to take time to build up in the body before users begin to feel their impact. But even then, says Barry Gordon, a neurology professor at the Johns Hopkins Medical Center, positive results wouldn’t necessarily constitute evidence of a pharmacological benefit.

Barbara Sahakian, a neuroscientist at Cambridge University, doesn’t dismiss the possibility of nootropics to enhance cognitive function in healthy people. She would like to see society think about what might be considered acceptable use and where it draws the line – for example, young people whose brains are still developing. But she also points out a big problem: long-term safety studies in healthy people have never been done. Most efficacy studies have only been short-term. “Proving safety and efficacy is needed,” she says.

Vinh Ngo, a San Francisco family practice doctor who specializes in hormone therapy, has become familiar with piracetam and other nootropics through a changing patient base. His office is located in the heart of the city’s tech boom and he is increasingly sought out by young, male tech workers who tell him they are interested in cognitive enhancement.

And the drugs are not terribly difficult to get, depending on where you’re located. Modafinil has an annual global share of $700 million, with high estimated off-label use. Although these drugs can be purchased over the internet, their legal status varies between countries. For example, it is legal to possess and use Modafinil in the United Kingdom without a prescription, but not in United States.

If this is the case, this suggests some thoughtfulness about my use of nicotine: there are times when use of nicotine will not be helpful, but times where it will be helpful. I don’t know what makes the difference, but I can guess it relates to over-stimulation: on some nights during the experiment, I had difficult concentrating on n-backing because it was boring and I was thinking about the other things I was interested in or working on - in retrospect, I wonder if those instances were nicotine nights.
Adderall is a mix of 4 amphetamine salts (FDA adverse events), and not much better than the others (but perhaps less addictive); as such, like caffeine or methamphetamine, it is not strictly a nootropic but a cognitive enhancer and can be tricky to use right (for how one should use stimulants, see How To Take Ritalin Correctly). I ordered 10x10mg Adderall IR off Silk Road (Wikipedia). On the 4th day after confirmation from seller, the package arrived. It was a harmless looking little padded mailer. Adderall as promised: 10 blue pills with markings, in a double ziplock baggy (reasonable, it’s not cocaine or anything). They matched pretty much exactly the descriptions of the generic I had found online. (Surprisingly, apparently both the brand name and the generic are manufactured by the same pharmacorp.)
If I stop tonight and do nothing Monday (and I sleep the normal eight hours and do not pay any penalty), then that’ll be 4 out of 5 days on modafinil, each saving 3 or 4 hours. Each day took one pill which cost me $1.20, but each pill saved let’s call it 3.5 hours; if I value my time at minimum wage, or 7.25/hr (federal minimum wage), then that 3.5 hours is worth $25.37, which is much more than $1.20, ~21x more.
One idea I’ve been musing about is the connections between IQ, Conscientiousness, and testosterone. IQ and Conscientiousness do not correlate to a remarkable degree - even though one would expect IQ to at least somewhat enable a long-term perspective, self-discipline, metacognition, etc! There are indications in studies of gifted youth that they have lower testosterone levels. The studies I’ve read on testosterone indicate no improvements to raw ability. So, could there be a self-sabotaging aspect to human intelligence whereby greater intelligence depends on lack of testosterone, but this same lack also holds back Conscientiousness (despite one’s expectation that intelligence would produce greater self-discipline and planning), undermining the utility of greater intelligence? Could cases of high IQ types who suddenly stop slacking and accomplish great things sometimes be due to changes in testosterone? Studies on the correlations between IQ, testosterone, Conscientiousness, and various measures of accomplishment are confusing and don’t always support this theory, but it’s an idea to keep in mind.

Because executive functions tend to work in concert with one another, these three categories are somewhat overlapping. For example, tasks that require working memory also require a degree of cognitive control to prevent current stimuli from interfering with the contents of working memory, and tasks that require planning, fluency, and reasoning require working memory to hold the task goals in mind. The assignment of studies to sections was based on best fit, according to the aspects of executive function most heavily taxed by the task, rather than exclusive category membership. Within each section, studies are further grouped according to the type of task and specific type of learning, working memory, cognitive control, or other executive function being assessed.

Those who have taken them swear they do work – though not in the way you might think. Back in 2015, a review of the evidence found that their impact on intelligence is “modest”. But most people don’t take them to improve their mental abilities. Instead, they take them to improve their mental energy and motivation to work. (Both drugs also come with serious risks and side effects – more on those later).
The research literature, while copious, is messy and varied: methodologies and devices vary substantially, sample sizes are tiny, the study designs vary from paper to paper, metrics are sometimes comically limited (one study measured speed of finishing a RAPM IQ test but not scores), blinding is rare and unclear how successful, etc. Relevant papers include Chung et al 2012, Rojas & Gonzalez-Lima 2013, & Gonzalez-Lima & Barrett 2014. Another Longecity user ran a self-experiment, with some design advice from me, where he performed a few cognitive tests over several periods of LLLT usage (the blocks turned out to be ABBA), using his father and towels to try to blind himself as to condition. I analyzed his data, and his scores did seem to improve, but his scores improved so much in the last part of the self-experiment I found myself dubious as to what was going on - possibly a failure of randomness given too few blocks and an temporal exogenous factor in the last quarter which was responsible for the improvement.
Ngo has experimented with piracetam himself (“The first time I tried it, I thought, ‘Wow, this is pretty strong for a supplement.’ I had a little bit of reflux, heartburn, but in general it was a cognitive enhancer. . . . I found it helpful”) and the neurotransmitter DMEA (“You have an idea, it helps you finish the thought. It’s for when people have difficulty finishing that last connection in the brain”).
According to clinical psychiatrist and Harvard Medical School Professor, Emily Deans, “there's probably nothing dangerous about the occasional course of nootropics...beyond that, it's possible to build up a tolerance if you use them often enough." Her recommendation is to seek pharmaceutical-grade products which she says are more accurate regarding dosage and less likely to be contaminated.

I have elsewhere remarked on the apparent lack of benefit to taking multivitamins and the possible harm; so one might well wonder about a specific vitamin like vitamin D. However, a multivitamin is not vitamin D, so it’s no surprise that they might do different things. If a multivitamin had no vitamin D in it, or if it had vitamin D in different doses, or if it had substances which interacted with vitamin D (such as calcium), or if it had substances which had negative effects which outweigh the positive (such as vitamin A?), we could well expect differing results. In this case, all of those are true to varying extents. Some multivitamins I’ve had contained no vitamin D. The last multivitamin I was taking both contains vitamins used in the negative trials and also some calcium; the listed vitamin D dosage was a trivial ~400IU, while I take >10x as much now (5000IU).

Hericium erinaceus (Examine.com) was recommended strongly by several on the ImmInst.org forums for its long-term benefits to learning, apparently linked to Nerve growth factor. Highly speculative stuff, and it’s unclear whether the mushroom powder I bought was the right form to take (ImmInst.org discussions seem to universally assume one is taking an alcohol or hotwater extract). It tasted nice, though, and I mixed it into my sleeping pills (which contain melatonin & tryptophan). I’ll probably never know whether the $30 for 0.5lb was well-spent or not.
Either prescription or illegal, daily use of testosterone would not be cheap. On the other hand, if I am one of the people for whom testosterone works very well, it would be even more valuable than modafinil, in which case it is well worth even arduous experimenting. Since I am on the fence on whether it would help, this suggests the value of information is high.
Brain-imaging studies are consistent with the existence of small effects that are not reliably captured by the behavioral paradigms of the literature reviewed here. Typically with executive function tasks, reduced activation of task-relevant areas is associated with better performance and is interpreted as an indication of higher neural efficiency (e.g., Haier, Siegel, Tang, Abel, & Buchsbaum, 1992). Several imaging studies showed effects of stimulants on task-related activation while failing to find effects on cognitive performance. Although changes in brain activation do not necessarily imply functional cognitive changes, they are certainly suggestive and may well be more sensitive than behavioral measures. Evidence of this comes from a study of COMT variation and executive function. Egan and colleagues (2001) found a genetic effect on executive function in an fMRI study with sample sizes as small as 11 but did not find behavioral effects in these samples. The genetic effect on behavior was demonstrated in a separate study with over a hundred participants. In sum, d-AMP and MPH measurably affect the activation of task-relevant brain regions when participants’ task performance does not differ. This is consistent with the hypothesis (although by no means positive proof) that stimulants exert a true cognitive-enhancing effect that is simply too small to be detected in many studies.

Cognition is a suite of mental phenomena that includes memory, attention and executive functions, and any drug would have to enhance executive functions to be considered truly ‘smart’. Executive functions occupy the higher levels of thought: reasoning, planning, directing attention to information that is relevant (and away from stimuli that aren’t), and thinking about what to do rather than acting on impulse or instinct. You activate executive functions when you tell yourself to count to 10 instead of saying something you may regret. They are what we use to make our actions moral and what we think of when we think about what makes us human.

Lebowitz says that if you're purchasing supplements to improve your brain power, you're probably wasting your money. "There is nothing you can buy at your local health food store that will improve your thinking skills," Lebowitz says. So that turmeric latte you've been drinking everyday has no additional brain benefits compared to a regular cup of java.
Table 1 shows all of the studies of middle school, secondary school, and college students that we identified. As indicated in the table, the studies are heterogeneous, with varying populations sampled, sample sizes, and year of data collection, and they focused on different subsets of the epidemiological questions addressed here, including prevalence and frequency of use, motivations for use, and method of obtaining the medication.

This is one of the few times we’ve actually seen a nootropic supplement take a complete leverage on the nootropic industry with the name Smart Pill. To be honest, we don’t know why other companies haven’t followed suit yet – it’s an amazing name. Simple, and to the point. Coming from supplement maker, Only Natural, Smart Pill makes some pretty bold claims regarding their pills being completely natural, whilst maintaining good quality. This is their niche – or Only Natural’s niche, for that matter. They create supplements, in this case Smart Pill, with the… Learn More...

When I worked on the Bulletproof Diet book, I wanted to verify that the effects I was getting from Bulletproof Coffee were not coming from modafinil, so I stopped using it and measured my cognitive performance while I was off of it. What I found was that on Bulletproof Coffee and the Bulletproof Diet, my mental performance was almost identical to my performance on modafinil. I still travel with modafinil, and I’ll take it on occasion, but while living a Bulletproof lifestyle I rarely feel the need.